We are investigating the genotoxic effects in rats of the metallic salts of cadmium, lead, and mercury, singly and in combination. The studies include the testing by ultrafiltration screening techniques of improved methods of chelation therapy using mixed ligand chelates. The cytogenetic investigations include the effects of the metals on chromosomal aberrations and chromosomal banding patterns in bone marrow and germ cells of the treated rats and their offspring. In addition, we plan to ascertain whether mixed ligand chelate therapy influences any observed chromosomal effects in both generations. A new and rapid method for obtaining cells for chromosomal analysis without the use of Colcemid has been developed. Cells can be obtained from the same animal during its lifetime, permitting sequential analyses. The toxic effects of the metals in various concentrations are being evaluated in terms of their LD50's expressed in units of micromolar/kg.